1. Field of the Invention
The present invention is an improved process for the asymmetric hydrogenation of a double bond.
2. Description of the Related Art
[R-(R*,R*)]-N-[3-[1-[5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl -2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-2-pyridinesulfonamide is a protease inhibitor useful in treating humans infected with the HIV virus (AIDS) and is known as tipranavir.
J. Am. Chem. Soc., 119, 3627 (1997) and the J. Org. Chem., 63, 7348 (1998) both disclose processes to produce tipranavir.
U.S. patent application Ser. No. 09/213,887 discloses a process to convert the ketone (I) to the cyclic ester (VI) as set forth in CHART A and EXAMPLES 1 thru 4 of U.S. patent application Ser. No. 09/213,887. CHART F of U.S. patent application Ser. No. 09/213,887 then discloses the transformation of the cyclic ester (VI) to the corresponding 6(R)- and 6(S)-olefin (XXV) by the process of EXAMPLE 16 which is then hydrogenated by the process of EXAMPLE 17 to produce the nitro-.alpha.,.beta.-unsaturated ester (XVII). The nitro-.alpha.,.beta.-unsaturated ester (XVII) is then transformed into tipranavir (XIX) by the process of EXAMPLES 14 and 15.
Hydrogenation reactions are very well known to those skilled in the art. In some hydrogenation reactions the product produced has an asymmetric carbon atom as in EXAMPLE 17 of U.S. patent application Ser. No. 09/213,887. It is known to those skilled in the art that the enantioselectivity of the hydrogenation can be influenced by the catalyst used. U.S. Pat. Nos. 5,171,892, 5,532,395 and 5,559,267 disclose enantioselective rhodium catalysts known as "DuPHOS" catalysts which can provide enantioselective hydrogenations in the 70 to 89% range.
U.S. Pat. No. 5,686,631 and Tetrahedron Lett. 37, 8321 (1996) disclose an asymmetric hydrogenation of warfarin, a 2-pyranone derivative, with 89% enantioselectivity with a DuPHOS catalyst. However, warfarin has a phenyl ring attached to the 5,6-position of the compounds of the present invention which would change the three dimensional nature of the compound. Chem. Rev. 93, 1307 (1993) and Chem. Int. Ed. Engl. 26, 190 (1987) disclose that an important feature in some stereoselective hydrogenation reactions is a secondary coordination of functional groups.
Catalytic Asymmetric Synthesis; VCH, New York, 1993, Chapter 1 and Asymmetric Catalysis in Organic Synthesis, Wiley & Sons, New York, 1993, Chapter 2 disclose an important feature of stereoselective hydrogenation of olefin substrates is the geometry (E or Z) of the double bond. It is known that one isomer of an olefin would be a preferred substrate to obtain higher enantioselectivity of a particular enantiomeric product.